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Original article A five-year antimicrobial resistance pattern observed in Shigella species isolated from stool samples in Gondar University Hospital, northwest Ethiopia

Gizachew Yismaw, Challa Negeri, Afework Kassu Abstract Background: Shigellosis is a global human health problem and an important public health problem, especially in developing countries, where substandard hygiene and unsafe water supplies abound. Besides, an increase in resistance against many different drugs among Shigella isolates has been observed in the last two decades. Objective: To determine the pattern of antimicrobial sensitivity of shigella species to commonly used antibiotics. Methods: The antibiotic susceptibility pattern of Shigella species isolated from stool specimens processed over five years at the bacteriology laboratory of the University of Gondar teaching hospital in northwest Ethiopia was investigated. Stool specimens were processed in accordance with the standard bacteriological methods and data were collected in the laboratory log book for bacterial culture, isolation and antimicrobial sensitivity. Results: From the total of 2,891 stool specimens that were cultured, 214 yielded Shigella species. The overall sensitivity of Shigella species to the commonly used antibiotics in the area was 92.1% to gentamicin, 91.1% to ciprofloxacin, 47.2% to chloramphenicol, 26.6% to cotrimoxazole, 20.1% to ampicillin and 14% to tetracycline. About 46% of the isolates were found to be resistant to at least three commonly used drugs, while 1.4% were found to be resistant to all the commonly used drugs. Conclusion: The results demonstrate the continued sensitivity of Shigella species to gentamicin and ciprofloxacin and their widespread resistance against tetracycline, ampicillin and cotrimoxazole. Based on our results, gentamicin and ciprofloxacin may be used rationally under strict regulation for the treatment of severe cases of shigellosis in case where other safer and better drugs are unavailable. [Ethiop.J.Health Dev. 2006;20(3):194-198] Introduction
tetracycline, and from 1.6% to 15.1% for chloram-
Shigellosis is a global human health problem. It is still an
important public health problem, especially in developing
countries, where there is substandard hygiene and unsafe
In Ethiopia, strains of Shigella that were resistant to
water supplies (1,2). Shigella still accounts for a many commonly used drugs have been reported in significant proportion of bacillary dysentery in many different parts of the country by several studies (12-14). tropical and subtropical countries (3,4). It is the most
In the aforementioned Ethiopian study reports, the strains
prevalent etiologic agent in childhood diarrhoea in most
were found to be most commonly resistant to tetracycline
countries (5,6). In Ethiopia, Shigelladysenteriae and (>80%), ampicillin (>65%), and cotrimoxazole (>70%). Shigellaflexineri have been identified as the species that
Multiple drug resistance to ampicillin, chloramphenicol,
account for about 80% of Shigella isolates (2).
tetracycline, and streptomycin was also very high in
those studies. Belay and his colleagues have reported a
The emergence of antimicrobial resistance to members of
strain that was resistant to eight drugs out of the nine
the Enterobacteriaceae family is posing serious problems
in the treatment of outbreaks of infections. Since its first
report in studies conducted in the 1950s, multiple-drug
Besides the temporal changes in the antibiogram of
resistance transmitted by plasmids among ShigellaShigella species, it is well known that antibiotic
species has been reported from many countries (6-8).
susceptibility patterns in Shigella may differ between
Moreover, an increase in resistance against many geographical areas. Such differences are never stable and different drugs has been observed in the last two decades.
may change rapidly especially in places where antibiotics
In one study, a significant decrease was observed in the
are used excessively (particularly in developing
susceptibility of the species to ampicillin and countries) (15). This warrants for frequent observation cotrimoxazole from 1988-89 to 1991-92 (9). In another
on the change in the pattern of antibiogram for this
report, it was shown that cotrimoxazole resistance of
Shigella increased from 3% to 40% within ten years time
(10). Another study showed that the percentage of To our knowledge, no report exists regarding the resistant Shigella strains in Madrid (Spain) increased antibiotic resistance pattern of Shigella species in Gondar from 39.6% to 97.9% for ampicillin, from 34.4% to region except one in the previous decade (16).This study 96.9% for cotrimoxazole, from 6.3% to 18.0% for was thus carried out to determine the pattern of
_______________________________________________________________________________________________ Department of Microbiology and Parasitology, College of Medicine and Health Sciences, University of Gondar, P. O. Box 196 Gondar, Ethiopia
A five year antimicrobial resistance pattern of Shigella species isolated from stool 195
_______________________________________________________________________________________ antimicrobial sensitivity of Shigella species to the most
(N=53, 24.8%) were from stool specimens collected from
commonly used antibiotics in Gondar, northwest in-patients. The distribution of the isolates in the different Ethiopia.
years was 45 (20.9%) in 2001, 23 (10.3%) in 2002, 34
(15.8%) in 2003, 85 (39.5%) in 2004, and 27 (14.6%) in
This retrospective study was conducted in the bacteriology laboratory of the University of Gondar The in vitro antimicrobial susceptibility pattern of Hospital, Gondar, Northwest Ethiopia, between Shigella isolates identified in the University of Gondar September 2001 and August 2005. The hospital is a Hospital from September 2001-August 2005 is shown in tertiary level teaching and referral hospital currently Table 1. About 46% of the Shigella isolates were found rendering health services for over 4 million rural and
to be resistant to at least three commonly used drugs, and
urban inhabitants in northwest Ethiopia.
1.4% of the Shigella isolates were found to be resistant to
all the commonly used drugs. Overall, many different
Stool specimens were collected from in- and out-patients
patterns of resistance were observed. The predominant
during the five year period and were processed following
resistance patterns to triple antibiotics were those to
the standard bacteriological methods (1). The stool A,T,Sxt (60.3%), A,T,C (46.3%), and A,C,Sxt (41.1%). specimens were inoculated on plates of MacConkey agar
The antibiogram resistance patterns for three up to six
(DIFCO) and Salmonella-Shigella agar (DIFCO). The antibiotics are depicted in Table 2. plates were incubated at 37oC for 24 hours and suspected
colonies were further examined by conventional The highest prevalence of antibiotic resistance was biochemical tests. Antimicrobial sensitivity testing was
documented to be against ampicillin 171 (79.9 %),
carried out by the standardized agar disk diffusion tetracycline 184 (86 %), and cotrimoxazole 157 (73.4%). techniques on Mueller Hinton agar (DIFCO) using the
The least resistance of antibiotics was observed to
following antimicrobial agents: ampicillin (A), ciprofloxacin 19(8.9%) and gentamicin 17(7.9%). Over tetracycline (T), cotrimoxazole (SXT), gentamicin (CN),
the years from 2001 to 2005, there was no significant
chloramphenicol (C), and ciprofloxacin (CIP) (17, 18).
increase in resistance to the individual antibiotics tested.
Turbidity of the broth was equilibrated to match with 0.5
Table 1: In vitro antimicrobial susceptibility pattern of Shigella species isolate in University of Gondar
The standard reference strains Escherichia coli ATCC
Hospital from September 2001 to August 2005
25922 and Pseudomonas aeruginosa ATCC 27853 were
Antibiotic Susceptible Resistant
tested as controls on the biochemical tests and agar plates
including Mueller Hinton with antibiotic discs. Data on
age, sex, source of specimens and culture results were
collected from the bacteriology log book. In this study,
multi-drug resistance was defined as simultaneous
resistance to three or more antimicrobial agents.
Statistical analysis was made using SPSS version 11.5
software. Ethical clearance was obtained from the Research and Publication office of the University of Table 2: Multiple drug resistance patterns among Gondar. Shigella species isolated in University of Gondar Hospital, north West Ethiopia, September 2001 to August 2005.
A total of 2891 stool specimens were received from in-
Resistance types Resistant isolates N (%)
patients (n=2371 (82%)) and out-patients (n=520 (18%))
and processed in the bacteriology laboratory over the five
years period. A total of 214 Shigella species were
isolated from the stool specimens, while 42 other entries
with incomplete data were excluded from the analysis.
Specimens cultured from children (up to 15 years of age),
adults aged between 16 to 45 years and those above 45
years accounted for 36.4%, 53.3%, and 10.3%,
respectively. One hundred fifteen (53.5%) of the isolates
were from male patients and the rest 99 (46.5%) were
from females. The majority of the Shigella species
(N=169, 75.2%) were isolated from specimens collected
from patients at the outpatient department and the rest
196 Ethiop.J.Health Dav______________________________________________________________________________________ Table 3: Comparison of resistance rate of Shigella species to commonly used antibiotics in different regions (Addis Ababa versus Gondar) and in different periods (1980, 1995, 2001-2005)Antibiotics 1980 1994-96 (Addis Ababa) 2001-2005 Gondar (Preset study Discussion
of gentamicin and related aminoglycosides (e.g.,
This retrospective study demonstrated a high level of
streptomycin) over the past five years (21-23). Since this
antimicrobial resistance pattern in Shigella species antibiotic appears to be less commonly used than the isolated from stool samples over a five year period in
orally administered antibiotics, the rate of resistance is
Gondar, northwest Ethiopia. The fact that the majority of
not yet high in this study as well as in other recent studies
Shigella isolates are from the pediatric population is from Bangladesh (24) and Sudan (25). Gentamicin and reported in the literature where 70% of all infections
ciprofloxacin are the only two commonly available
occur in children younger than 15 years (19). In the
antibiotics to which the majority of Shigella strains in
present work, children accounted for more than a third
Gondar area were susceptible as seen from the present
(36.4%) of all Shigella positive patients.
study. Although ciprofloxacin is contraindicated for those
patients below 18 years of age, gentamicin can still be
In line with our findings, a low rate of resistance to
used in settings where safer drugs are not available.
gentamicin and ciprofloxacin was observed in different
studies (4, 14). For example, Moez and his colleagues
Of the Shigella isolates, 90.8% were found to be resistant
observed a 3.1% resistance to ciprofloxacin (4). A recent
to one or more antimicrobial agent(s), and 87.8% were
prospective study conducted in southern Ethiopia showed
multi-drug resistant. The most common resistance was to
a high sensitivity of Shigella isolates to gentamicin (14).
tetracycline (73.5%) and cotrimoxazole (70.4%) as was
observed by other authors (4, 14). A high rate of
Resistance to cotrimoxazole, one of the drugs used in the
resistance of Shigella species was also observed for
treatment of shigellosis was first reported in Ethiopia in
cotrimoxazole (87.75%) and ampicillin (55.5%) in
1981 (20). Prior to this period, all strains isolated in
Pakistan and Nigeria (3, 26). On the contrary, Khan-
Addis Ababa were found to be sensitive to cotrimoxazole
Mohammed and his coworkers have found a low level of
and gentamicin (20). However, Belay and his colleagues
resistance to the above antibiotics as only 8.1% of the
(14) demonstrated a 55% resistance of Shigella strains to
isolates exhibited resistance to ampicillin, 2.7% to
cotrimoxazole. Although Khan-Mohammed et al (5) chloramphenicol, and 2.7% to cotrimoxazole (5). showed a 2.7% resistance rate in Trinidad, our finding of
a 73% resistance rate of the isolates to this antibiotic was
In this study, multiple drug resistance to as many as five
in agreement with observations from Pakistan (3) and
and six antibiotics was observed. Similar findings were
Iran (4) where a resistance rate of 70.4% and 87.8%,
seen in other studies from other localities in Ethiopia (12-
respectively, by Shigella species to cotrimoxazole was
14, 20). Shigella isolates from Sudanese patients with
diarrhoea also showed high resistance rates against the
commonly used antimicrobial agents: ampicillin,
In northwest Ethiopia, the resistance of Shigella species
chloramphenicol, tetracycline, cotrimoxazole, and
to cotrimoxazole is high and has slightly increased in
sulfonamide (25). Another study conducted in six
comparison to the previous report (16) (Table 3). countries in the East African region also showed Unfortunately, the drug is still commonly prescribed and
resistance of Shigella isolates to the commonly used
used by the community for diarrhoeal diseases, antibiotics except for nalidixic acid (27). A WHO particularly in children, and on the bases of self scientific working group had reported a high prevalence prescription from private pharmacies (21-23). Therefore,
of resistance to A, C, T and Sxt in developing countries
the fact that the majority of Shigella isolates were because of the very high consumption of antibiotics from resistant to cotrimoxazole is depressing since this drug is
the open market in these countries (15). Similarly, this
one of the drugs of choice in many countries (19) antibiogram was also common in our setting accounting including Ethiopia.
for 40% of the isolates (Table 2). Yet, the current
treatment of choice for shigellosis are still co-
Compared to a previous report from Gondar (16), a four
trimoxazole, ampicillin and ciprofloxacin (19,28).
fold increase in resistance to gentamicin was observed in
the present study (from 2% to 7.9%) (Table 3). This
Shigella are notorious for the rapid emergence and spread
increase might be because of the relatively increased use
of multiple drug resistance among strains and resistance
A five year antimicrobial resistance pattern of Shigella species isolated from stool 197
_______________________________________________________________________________________ patterns observed among strains of any one species in a
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